Search

Background: The aim of the study was to investigate the baseline characters that influence 3-month clinical outcomes in patients with acute ischemic stroke (AIS) after thrombolytic therapy. Methods: We consecutively enrolled 241 AIS patients who are treated with thrombolytic therapy with recombinant tissue plasminogen activator. Baseline characters were measured on admission including the National Institutes of Health Stroke Scale (NIHSS), Trial of Org 10172 in Acute Stroke Treatment (TOAST), risk factors, platelet indices, and lipid parameters. The subjects were divided into good or poor functional outcomes based on modified Rankin Scale at 3 months. The multivariate logistic regression was performed to explore the association between baseline factors and outcomes. Pearson correlation was used to investigate whether linear associations existed between platelet indices in different outcomes. Results: Multivariate logistic regression analysis showed that the NIHSS, TOAST classification, diabetes, mean platelet volume (MPV) are important factors for predicting clinical outcomes after 3 months in AIS patients. We found a correlation between elevated MPV and worse outcome at 3 months, particularly in large-artery atherosclerosis stroke patients. MPV and platelet count are negative correlated (r = −0.375, p = 0.000). MPV and platelet-to-lymphocyte ratio (PLR) (r = 0.83, p = 0.000), MPV and platelet distribution width (PDW) (r = 0.820, p = 0.000) both have highly positive linear correlations in patients with good outcome. Conclusions: Overall, lower NIHSS and MPV levels on admission were predictors of good functional outcomes in patients with AIS after undergoing thrombolytic therapy. The correlations between MPV, PDW, and PLR may be helpful to evaluate prognosis in stroke patients and deserve further exploration.

Diffusion tensor imaging (DTI) studies have revealed distinct white matter (WM) characteristics of the brain following diseases. Beyond the lesion‐symptom maps, stroke is characterized by extensive structural and functional alterations of brain areas remote to local lesions. Here, we further investigated the structural changes over a global level by using DTI data of 10 ischemic stroke patients showing motor impairment due to basal ganglia lesions and 11 healthy controls. DTI data were processed to obtain fractional anisotropy (FA) maps, and multivariate pattern analysis was used to explore brain regions that play an important role in classification based on FA maps. The WM structural network was constructed by the deterministic fiber‐tracking approach. In comparison with the controls, the stroke patients showed FA reductions in the perilesional basal ganglia, brainstem, and bilateral frontal lobes. Using network‐based statistics, we found a significant reduction in the WM subnetwork in stroke patients. We identified the patterns of WM degeneration affecting brain areas remote to the lesions, revealing the abnormal organization of the structural network in stroke patients, which may be helpful in understanding of the neural mechanisms underlying hemiplegia., We identified the patterns of white matter degeneration affecting brain areas remote to the lesions, revealing the abnormal organization of the structural network in stroke patients, which may be helpful in understanding of the neural mechanisms underlying hemiplegia.

Stroke is one of the highest incidence neurological disorder with great morbidity and mortality rate. The secondary neuroinflammation contributed by microglial activation is a consequential response observed in the pathogenesis of stroke. High-mobility group box 1, a non-histone nuclear protein, interacts with immune cells, such as microglia, and leads to a cascade amplification of the secondary neuroinflammatory responses, which are related to neuronal damage later. Melatonin is a neurohormone, well-known as its anti-oxidative and anti-inflammatory effects. However, until now, more findings are required for better understanding about anti-inflammatory effect of melatonin on HMGB1 and HMGB1-triggered pathway in LPS-induced microglial activation. Melatonin effect on the viability of BV2 microglial cells was measured by CCK-8 assay; mRNA levels of HMGB1 and other inflammatory cytokines were determined by quantitative real-time polymerase chain reaction assay or enzyme-linked immunosorbent assays; the protein expression levels of TLR4/MyD88/NF-κB and SIRT1 were detected by Western blot, and HMGB1 translocation and release from BV2 microglial cells were examined by immunofluorescence assay. The results of this study demonstrated that melatonin suppressed LPS-triggered BV2 microglial activation-mediated inflammation by inhibiting high expression and release of HMGB1 and moderating the activation of subsequent TLR4/MyD88/NF-κB signaling pathway, which was activated by SIRT1 elevation. Furthermore, LPS-induced expression of pro-inflammatory cytokines (i.e., TNF-α, IL-6, and IL-1β) was notably reversed by melatonin pre-treatment. In summary, our findings suggest that melatonin may act as a promising therapeutic agent for reducing post-stroke neuroinflammation by targeting HMGB1 and the subsequent signaling axis.

A health program aiming at college students is pressingly needed to improve their lifestyle and prevent diseases. However, a health intervention often requires health facilities and the many efforts of health workers. This project attempts to evolve traditional health intervention by using integrated methods based on social media and multiple mobile tools. A total of 110 undergraduates from Zhejiang University were recruited. In all, 87 participants volunteered to enroll in the intervention group, whereas 23 stayed in a control group. Fifteen staff (dietitians, health assistants and a sports coach) used the WeChat app and its plugin Zhishi mini-program for health education, diet and physical activity (PA) supervision during 21 days. Pre-to-post changes of eating habits, physical fitness tests and anthropometry data were measured. The RE-AIM framework was employed to evaluate the intervention, dimensions of which were Reach, Effectiveness, Adoption, Implementation, and Maintenance. The recruitment rate of students was 79.1%. The intervention group showed significant progress in terms of healthy food intake (all P

Liver X receptors (LXRs) have recently been reported to be novel and potential targets for the reversal of depressive-like behaviors, but the mechanism remains unclear. Hippocampal neuroinflammation and impairment of the normal structure and function of microglia are closely associated with depression. To investigate the effects of LXRs agonist (GW3965) on neuroinflammation and microglia in the hippocampal formation of mice with chronic unpredictable stress (CUS)-induced depression, depressive-like behaviors were evaluated by behavioral tests, hippocampal LXRs gene expression were evaluated by qRT-PCR, the protein expression levels of interleukin-1β, tumor necrosis factor-α, inducible nitric oxide synthase, nuclear factor kappa B, and cluster of differentiation 206 were estimated by western blotting, modern stereological methods were used to precisely quantify the total number of microglia in each hippocampal subregion, and immunofluorescence was used to detect the density of activated microglia and the morphology of microglia. We found that GW3965 alleviated the depressive-like behavior induced by CUS, reversed the decrease in hippocampal LXRα and LXRβ induced by CUS, increased the protein expression of pro-inflammatory factors, and decreased the protein expression of antiinflammatory factors induced by CUS. Moreover, CUS intervention significantly increased the number of microglia in the CA1 region, CA2/3 region, and dentate gyrus and the density of activated microglia in the CA2/3 region and dentate gyrus and significantly decreased the endpoints of microglial branches and process length of microglia in the dentate gyrus, while 4 weeks of injections with GW3965 reversed these changes. These findings suggest that regulating the number, activated state, and morphology of microglia in hippocampal subregions might be an important basis for the antidepressant effects of LXRs.

Many neuroimaging studies have reported that stroke induces abnormal brain activities. Yet, little is known about resting-state networks (RSNs) and the corresponding white matter changes in stroke patients with hemiplegia. Here, we utilized functional magnetic resonance imaging (fMRI) to measure the neural activity and related fiber tracks in 14 ischemic stroke patients with hemiplegia and 12 healthy controls. The fractional amplitude of low-frequency fluctuations (fALFF) calculation and correlation analyses were used to assess the relationship between the regional neural activity and movement scores. Tractography was performed using the diffusion tensor imaging (DTI) data to analyze the fibers passing the regions of interest. Compared with controls, stroke patients showed abnormal functional connectivity (FC) in some brain regions of the RSNs. The fALFF was increased in the contralesional parietal lobe, with the regional fALFF being correlated to behavioral scores in stroke patients. And the tracked fibers across regions with reduced FC in the RSNs were increased in stroke patients. The study suggested that structural remodeling of functionally-relevant white matter tracts probably be an adaptive response that compensates for injury to the brain.

Cognitive impairment can seriously affect the quality of life of Parkinson's disease (PD) patients. Although numerous studies showed that N200, P300 latency and amplitude are correlated with cognitive functions, there is a sufficient amount of controversial results. Therefore, it is necessary to conduct a meta-analysis of N200, P300 latency and amplitude data of event-related potential (ERP) in PD.We systematically searched on PubMed and Web of Science for PD-related ERP studies published before December 2021. Standard mean difference (SMD) and 95% confidence interval (CI) estimates of N200 and P300 components were compared among PD patients, PD dementia (PDD) patients, PD non-dementia (PDND) patient, and healthy control (HC).Our meta-analysis showed prolonged N200 latency at the Fz, Cz electrode sites, prolonged P300 latency at the Fz sites in PD patients, compared to HC; prolonged N200 latency at the Cz, Pz electrode sites in PDND patients, compared to HC; prolonged P300 latency at the Cz site in PDD patients, compared to PDND patients; and reduced P300 amplitude at the Fz electrode site in PDND patients, compared to HC.N200 and P300 component may be potential electrophysiological biomarkers of early cognitive impairment in PD patients. Future studies are needed to confirm this conclusion. Estimates of N200 and P300 component can be a valuable support for clinicians in diagnosis of early cognitive impairment in PD patients due to the simplicity and non-invasiveness of the procedure.

We aimed to identify the active ingredients and elucidate the underlying mechanism of action of Atractylodes lancea (Thunb.) DC (namely, Cangzhu) for the treatment of gouty arthritis (GA) based on network pharmacology methods. These findings are expected to provide a theoretical basis for the clinical treatment of GA.We used monosodium urate (MSU)-induced GA rats as a model to test the overall efficacy of Cangzhu in vivo. Then, the components of the Cangzhu decoction were analyzed and identified, and we screened the active ingredients and their targets. The GA disease targets were predicted by GeneCards and Disgenet databases and found to overlap in both databases. The STRING database was used to construct a protein-protein interaction network, followed by identification of the hub genes using Network Analyzer. Thereafter, Cytoscape software (version 3.8.2) was applied to construct a network for drug-active ingredient-key targets. Next, we applied cluego, a plug-in of Cytoscape, to perform gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway enrichment analyses. Additionally, molecular docking was used to verify the characteristics of the key candidate components interacting with the hub therapeutic targets. Finally, we established an inflammatory injury model of LPS using RAW264.7 macrophages and used it to experimentally validate the critical active ingredients.Cangzhu effectively protected against gouty arthritis in vivo, and network pharmacology results revealed various active ingredients in Cangzhu, such as wogonin, atractylenolide I and atractylenolide II. These compounds were found to act on 16 hub targets, including tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin-1β (IL-1β), prostaglandin-endoperoxide synthase 2 (PTGS2), recombinant mitogen-activated protein kinase 14 (MAPK14) and transcription factor p65 (RELA), which have significant effects on regulating inflammatory factors and apoptosis-related pathways to improve the proinflammatory or anti-inflammatory imbalance in the body, and this may be one of the underlying mechanisms of Cangzhu in anti-GA.Our findings revealed that Cangzhu comprises multiple active components that exert various targeted effects during GA treatment. These findings provide relevant insights to illuminate the mechanism of Cangzhu in the treatment of GA and provide a reference for further experimental research.

Hippocampal dysfunction related to cognitive impairment and emotional disorders in young children and adolescents caused by neonatal hypoxic-ischemic brain injury (HIBI) has attracted increasing attention in recent years. Crosstalk between the nervous and immune systems organized by hypoxia-ischemia (HI) insult may contribute to hippocampal dysfunction after HIBI. Extracellular HMGB1 functions as a damage-associated molecular pattern to instigate and amplify inflammatory responses, but whether this molecule is correlated with hippocampal dysfunction after HIBI is largely unknown. Therefore, this study examined hippocampal function after HMGB1 inhibition in an experimental HIBI model to verify the hypothesis that HMGB1 is a key mediator of hippocampal neuropathology in neonatal HIBI. By administering different doses of the HMGB1-specific inhibitor glycyrrhizin (GLY), we first found that GLY reversed the HI insult-induced loss of neurons and myelin in the hippocampal region and neurobehavioral impairments, partially in a dose-dependent manner, and based on this, we determined the optimal drug concentration to be 50 mg/kg. Subsequent analysis found that this neuroprotective effect was achieved through the inhibition of HMGB1 expression and nucleocytoplasmic translocation, a reduction in the abnormal expression of proteins associated with the downstream signaling pathway of HMGB1, a decrease in the inflammatory response, the suppression of increases in microglia/astrocytes, and the inhibition of hippocampal cell apoptosis. Collectively, our discoveries contribute to the rising appreciation of the role of HMGB1 in the neuropathology of hippocampal dysfunction and related behavioral outcomes following HIBI.

In this work, a new Ni(II)-based coordination polymer (CP) with the chemical formula of {[(Ni)2(L1)(L2)(H2O)2](DMF)2}n (1, H4L1 = 5-((3,5-dicarboxybenzyl)oxy)isophthalic acid, L2 = 2,4,6-tr...

Reprogramming of fibroblasts into induced cardiomyocytes (iCMs) is a potentially promising strategy for regenerating a damaged heart. However, low conversion rate of fibroblasts to cardiomyocytes and poor in vivo application efficacy are major challenges in this reprogramming process. To address this issue, we attempted to identify small molecules related to histone acyl post-translational modifications that could enhance the reprogramming ability towards cardiac fate. Using α-muscle heavy chain-GFP-tagged mouse embryo fibroblasts as a starting cell type, we screened 46 inhibitors target histone acyl post-translational modifications and related epigenetic factors and identified an important role of Brd4 in modulating iCM reprogramming. In particular, we observed that a novel Brd4 degrader repressed many genes involved in immune responses especially JAK/STAT pathway. Mechanically, Brd4 degrader repressed JAK/STAT related gene expressions by affecting Brd4 binding to promoters of those genes. More importantly, Brd4 degrader treatment enhanced MGT induced cardiac regeneration in vivo and markedly improved myocardial performance after myocardial infarction. These findings shed new light on the molecular mechanisms underlying the cardiac conversion of fibroblasts and provide novel targets and small molecules to improve iCM reprogramming for clinical applications.

To compare the e!cacy and functional outcomes of dl-3-n-Butylphthalide (NBP) and human urinary kallidinogenase (HUK) on ischemic stroke patients and to determine their effects on serum tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor (VEGF).A prospective study was conducted on 57 ischemic stroke patients. Functional outcomes were assessed by the National Institute Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), and the activities of daily living score (ADL), whereas TNF-α and VEGF expressions were measured by enzyme-linked immunosorbent assay (ELISA).TNF-α was significantly down-regulated in the NBP group and upregulated in the control group two weeks after treatment (Both treatments are effective and can significantly promote recovery in stroke patients. Additionally, both options have similar effects in promoting long-term recovery, with NBP exerting a greater impact on serum VEGF and TNF-α expressions.

Diffusion tensor imaging (DTI) studies have revealed distinct white matter characteristics of the brain following diseases. Beyond the lesion-symptom maps, stroke is characterized by extensive structural and functional alterations of brain areas remote to local lesions. Here, we further investigated the structural changes over a global level by using DTI data of ten ischemic stroke patients showing motor impairment due to basal ganglia lesions and 11 healthy controls. DTI data were processed to obtain fractional anisotropy (FA) maps, and multivariate pattern analysis (MVPA) was used to explore brain regions that play an important role in classification based on FA maps. The white matter (WM) structural network was constructed by the deterministic fiber-tracking approach. In comparison with the controls, the stroke patients showed FA reductions in the perilesional basal ganglia, brainstem, and bilateral frontal lobes. Using network-based statistics (NBS), we found a significant reduction in the WM subnetwork in stroke patients. We identified the patterns of WM degeneration affecting brain areas remote to the lesions, revealing the abnormal organization of the structural network in stroke patients, which may be helpful in understanding of the neural mechanisms underlying hemiplegia.

Objectives Progressive weakness of respiratory muscle is common to patients with amyotrophic lateral sclerosis, which leads to respiratory failure, even death. The evaluation of respiratory muscle is essential to evaluate the severity during the progression of the disease and choose appropriate interventions. This study aimed to evaluate the respiratory muscles change of the patients with amyotrophic lateral sclerosis by regular chest computed tomography. Methods The cross-sectional area of respiratory muscles in amyotrophic lateral sclerosis patients was retrospectively reviewed. The severity of the disease was determined by the value of the amyotrophic lateral sclerosis function score scale. A healthy control group was selected with well-matched to the amyotrophic lateral sclerosis patients. Results Compared with the healthy control group, the cross-sectional area of the diaphragm muscle was lower in amyotrophic lateral sclerosis patients. The reduced cross-sectional area of respiratory muscles has a positive correlation with a lower amyotrophic lateral sclerosis function score. Patients with amyotrophic lateral sclerosis further showed a significant reduction in the cross-sectional area of respiratory muscles after 6-8 months.Conclusions The single-slice axial computed tomography is a fast and reliable method to quantitatively assess the cross-sectional area of respiratory muscles, especially diaphragm muscle, in disease progression.

Background. Ketamine has been shown to possess lasting antidepressant properties. However, studies of the mechanisms involved in its effects on poststroke depression are nonexistent. Methods. To investigate these mechanisms, Sprague-Dawley rats were treated with a single local dose of ketamine after middle cerebral artery occlusion and chronic unpredicted mild stress. The effects on the hippocampal dentate gyrus were analyzed through assessment of the N-methyl-D-aspartate receptor/calcium/calmodulin-dependent protein kinase II (NMDAR/CaMKII) pathway, synaptic plasticity, and behavioral tests. Results. Ketamine administration rapidly exerted significant and lasting improvements of depressive symptoms. The biochemical analysis showed rapid, selective upregulation and downregulation of the NMDAR2-β and NMDAR2-α subtypes as well as their downstream signaling proteins β-CaMKII and α-phosphorylation in the dentate gyrus, respectively. Furthermore, the colocalization analysis indicated a significant and selectively increased conjunction of β-CaMKII and postsynaptic density protein 95 (PSD95) coupled with a notable decrease in NMDAR2-β association with PSD95 after ketamine treatment. These changes translated into significant and extended synaptic plasticity in the dentate gyrus. Conclusions. These findings not only suggest that ketamine represents a viable candidate for the treatment of poststroke depression but also that ketamine’s lasting antidepressant effects might be achieved through modulation of NMDAR/CaMKII-induced synaptic plasticity in key brain regions.

E-commerce, driven by the technological advances of the semiconductor industry, becomes one of the fastest-growing industries and has become the largest sector of the electronics industry in recent years. Compared with the traditional offline business, E-commerce business eliminates geographical limitations by allowing consumers to purchase anywhere. Additionally, E-commerce only requires a web-based platform to start a business, resulting in a lower investment or business capital. Based on more than 75,000,000 transactions of one E-commerce company from January 2013 to June 2019, we analyze the economic impact of the holiday season, the relationship between price and sales, etc. Furthermore, we utilize Artificial Intelligence (AI) techniques to predict the sales of products. Here, assemble learning models, including Catboost, GBDT, LightGBM, and XGBoost, are adopted for regression prediction. The results show that Cat boost performs better than other methods.

Background: Diffusion tensor imaging (DTI) studies have revealed distinct white matter characteristics of the brain following diseases. Beyond the lesion-symptom mapping, recent studies have demonstrated extensive structural and functional alterations of remote areas to local lesions caused by stroke in the brain. Here, we further investigated the structural changes from a global level using DTI data through multivariate pattern analysis (MVPA) and network-based statistic (NBS). Methods: Ten ischemic stroke patients with basal ganglia lesions and motor dysfunctions and eleven demographically matched adults as controls underwent brain Magnetic Resonance Imaging scans. DTI data were processed to obtain fractional anisotropy (FA) maps and MVPA was used to explore brain regions that play an important role in classification based on FA maps. The white matter (WM) structural network was constructed by the deterministic fiber tracking approach according to the Automated Anatomical Labeling (AAL) atlas. NBS was used to explore differences in structural networks between groups.Results: MVPA applied to FA images correctly identified stroke patients with a statistically significant accuracy of 100% (P≤0.001). Compared with the controls, the study patients showed FA reductions in the perilesional basal ganglia and brainstem, with a few showing reductions in bilateral frontal lobes. Using NBS, we found a significant decrease in FA-weighted WM subnetwork in stroke patients. Conclusions: We identified some patterns of WM degeneration affecting brain areas remote to the ischemic lesion, revealing the abnormal organization of WM network in stroke patients, which may be helpful for the understanding of the neural mechanisms of stroke sequela.

Background: Diffusion tensor imaging (DTI) studies have revealed distinct white matter characteristics of the brain following diseases. Beyond the lesion-symptom mapping, recent studies have demonstrated extensive structural and functional alterations of remote areas to local lesions caused by stroke in the brain. Here, we further investigated the structural changes from a global level using DTI data through multivariate pattern analysis (MVPA) and network-based statistic (NBS). Methods: Ten ischemic stroke patients with basal ganglia lesions and motor dysfunctions and eleven demographically matched adults as controls underwent brain Magnetic Resonance Imaging scans. DTI data were processed to obtain fractional anisotropy (FA) maps and MVPA was used to explore brain regions that play an important role in classification based on FA maps. The white matter (WM) structural network was constructed by the deterministic fiber tracking approach according to the Automated Anatomical Labeling (AAL) atlas. NBS was used to explore differences in structural networks between groups. Results: MVPA applied to FA images correctly identified stroke patients with a statistically significant accuracy of 100% (P≤0.001). Compared with the controls, the study patients showed FA reductions in the perilesional basal ganglia and brainstem, with a few showing reductions in bilateral frontal lobes. Using NBS, we found a significant decrease in FA-weighted WM subnetwork in stroke patients. Conclusions: We identified some patterns of WM degeneration affecting brain areas remote to the ischemic lesion, revealing the abnormal organization of WM network in stroke patients, which may be helpful for the understanding of the neural mechanisms of stroke sequela.

Little is known about the effect of astroglial GLT-1 of post-stroke depression (PSD) rat model on the function of neural stem cells (NSCs). This study aimed to investigate whether astroglial GLT-1 of PSD rats affect differentiation of NSCs from neonatal rat hippocampus and synaptic formation of NSC-derived neurons. Astrocytes were isolated from the left hippocampus of normal adult SD rats and PSD rats. A lentiviral vector was used to silence the expression of GLT-1 in astrocytes of PSD rats. NSCs were respectively co-cultured with normal (control), PSD, and GLT-1 silenced astrocytes for 7 days. GLT-1, GFAP, MAP2, Synaptophysin (SYN), glutamate (Glu) and glutamine (Gln) were respectively measured by qRT-PCR, western blot, immunofluorescence and efficient mass spectrometry (MS). PSD astrocytes increased the number of NSC-derived astrocytes, but inhibited the expression of GLT-1 of NSC-derived astrocytes and synapses of NSC-derived neurons. On the basis of the low expression of GLT-1 in PSD astrocytes, we further silenced GLT-1 in PSD astrocytes. Interestingly, GLT-1 silenced PSD astrocytes more obviously inhibited synapses of NSC-derived neurons, but increased the number of NSC-derived neurons and reversed the expression of GLT-1 in NSC-derived astrocytes. At the same time, concentration of glutamate in the medium elevated, and glutamine in the medium gradually reduced. In NSC-derived neurons and astrocytes, glutamate metabolism was also affected by changed GLT-1. Down-expressed GLT-1 in PSD astrocytes stimulated NSCs differentiating into astrocytes, but inhibiting the formation of functional synapses by influencing glutamate metabolism in vitro.

OBJECTIVES Inflammation plays a key role in the pathogenesis and progression of ischemic stroke (IS). The high mobility group box 1 (HMGB1) nucleoprotein is involved in the amplification of inflammatory responses during acute ischemic injury. HMGB1 levels in patients with active disease are higher than those in healthy controls. We performed a meta-analysis to assess currently published data pertaining to circulating blood HMGB1 levels in IS and the relationship with stroke severity. METHODS We systematically searched for studies investigating the circulating blood HMGB1 levels in patients with IS in PubMed/Medline, Embase, the Cochrane Library, Web of science and China National Knowledge Infrastructure (CNKI). Two independent researchers used the Cochrane Collaboration tools for data extraction and quality assessment. Extracted data were analyzed by Review Manager version 5.3. RESULTS A total of 28 studies were included with a total of 4497 participants, including 2671 IS patients and 1826 matched controls. The meta-analysis revealed that compared with control, IS patients had higher circulating blood HMGB1 levels (n = 4497, standardized mean difference (SMD) = 5.70, 95%confidence interval (CI) = 4.79 to 6.62, Z = 12.23, P